Metabolic dysregulation is central to the pathogenesis of diabetes and obesity. The Metabolic Pathophysiology Core (MPC) provides services to comprehensively phenotype metabolic processes in mouse models. The MPC has three Subcores: Metabolic Regulation, Tissue and In Vivo Imaging and Bariatric Surgery. The Metabolic Regulation Subcore provides tools to accurately assess metabolism in healthy, conscious, unstressed mice. This Subcore uses unique skills in chronically implanting catheters into the carotid artery and jugular vein to perform glucose clamps in the mouse. In addition, it has developed techniques to catheterize the portal vein and stomach to deliver hormones and nutrients by their physiologic routes. This Subcore also provides services to assess the components of energy balance (energy expenditure, food intake, activity, body composition). The MPC provides not only standardized tests for metabolic and endocrine assessments, but is also able to adapt using more sophisticated protocols. Additional services include in vitro organ perfusion techniques (liver, pancreas, hindlimb). It partners with VDRTC Islet Procurement and Analysis Core to provide high quality islets to investigators as well as tools to characterize islet function. The Tissue and In Vivo Imaging Subcore offers novel imaging technology to study metabolic processes in real time at the molecular level. Resources ofthis Subcore include: 1) a multi-photon excitation confocal microscope to visualize real time kinetics of calcium, NAD(P)H, and pH and fluorescent probes in cells and in situ whole organ preparations; and 2) bioluminescence imaging, to assay real-time kinetics of gene expression in intact mice by combining luciferase as a reporter gene with a highly sensitive optical single photon detection system. The Bariatric Surgery Subcore provides mice with restrictive or bypass surgical procedures that recapitulate the surgical procedures performed in humans for weight loss. The MPC, by virtue of its novel subcores, provides state-of-the-art technology to delineate the mechanism for the phenotypic expression of metabolic disorders in mice.